Triglycerides of medium-chain length fatty acids, known as medium-chain triglyceride(s) or MCT(s), can be synthesized by esterifying glycerol with fatty acids of carbon chain lengths of C8 (octanoic acid or caprylic acid) or C10 (decanoic acid or capric acid). MCTs are usually commercially available as a mixture of glycerol esters of C8 and C10 fatty acids, with small amounts (≦1% of each) of glycerol esters of C6 (hexanoic acid or caproic acid) and C12 (dodecanoic acid or lauric acid).
MCTs and their constituent medium-chain fatty acids are nontoxic materials which are used in the food and pharmaceutical industries. For example, Traul K. A. et al. (Food and Chemical Toxicology 38:79-98, 2000) state that MCTs have been utilized in an increasing number of food and nutrition applications. Also, it was reported by Roach, R. R. (Cereal Chem. 73(2):197-98, 1996) that tricaprin (triglyceride of C10), usually in mixtures with tricaprylin (triglycerides of C8), is used as an antifoaming and antistatic agent for plastics, lubricants, water treatment, and release agents for bakery products and candies. In addition, MCTs are also used primarily as emulsifiers in various human and veterinary pharmaceutical preparations and in cosmetics. U.S. Pat. No. 7,745,488 describes the use of medium-chain fatty acids or metallic salts or triglycerides or MCTs as an inducer of hematopoiesis. There are a number of toxicology studies which support the safety of MCTs. For example, the safety of human dietary consumption of MCTs, up to 1 g/kg, has been confirmed in several clinical trials. In fact, according to part 170 of the Code of Federal Regulations (CFR), the U.S. Food and Drug Administration (FDA) has granted triglycerides of fatty acids as GRAS (Generally Recognized As Safe) status for use as a food ingredient. Also, a literature review regarding the use of triglycerides such as tricaprin or tricaprylin in cosmetics supported the safety of these compounds (International Journal of Toxicology 2001, (20), 61-94). Similarly, the Cosmetic Ingredient Review (CIR) Expert Panel concluded that tricaprin and tricaprylin are safe with regard to the present practices of use and concentration in cosmetics (Elder, R. L. et al. J. Environ. Pathol. Toxicol. 4: 105-120, 1980). U.S. Pat. No. 4,602,040 describes another application of MCTs as a pharmaceutical excipient. More recently, MCTs were used for formulating existing drugs for enhancement of palatability and stability (Pharmaceutical Development and Technology, 2003, Vol. 8, (1), 111-115) or for improvement of drug distribution/solubility profile. In fact, the use of triglycerides for formulation of poorly water-soluble drugs has been investigated by different approaches which include nanoparticles, micelles and emulsions. For example, the oral bioavailability of the slightly water-soluble drug anethole trithione was enhanced by use of an MCT sub-microemulsion formulation (Si-Fei, H et al., International Journal of Pharmaceutics 2009, 379 (1), 18-24). Also, the antitumor efficacy and absorption of the poorly water soluble cancer drug paclitaxel has been improved by the use of MCT as a vehicle (Hong, J. W. et al. Mol. Cancer Ther. 2007, 6(12) 3239-47; US patent application 2006/0104999).
As typically known in the art, the MCTs are obtained by the reaction of glycerol with medium-chain length fatty acids in the presence of an acid and at high temperature (140-260° C.) or with the use of an enzyme such as lipase at 70-90° C. The low purity of the triglyceride obtained by these known techniques necessitates decolourization and chromatographic purification/distillation which makes large-scale synthesis difficult. In general, the yield and the purity obtained by these known techniques does not exceed 75% due to incomplete esterification and the loss of the product during workup and purification.
There is a need for improving the yield of synthesis of MCTs. There is also a need for simplifying its process of preparation in view of large-scale preparation.